Innolign Biomedical has developed a novel microtissue system for assessing potential drug cardiotoxicities using technologies that allow for the creation of miniaturized human tissue constructs and the measurement their biomechanical activity. The goal of this Phase I SBIR proposal is to establish the feasibility of using these microfabricated arrays of engineered 3D human cardiac microtissues, termed CardioMicroTug, in a novel, high-throughput format for assessing cardiotoxicity of drugs. Cardiac toxicity represents a significant pharmaco-economic problem in the development of new drugs and biopharmaceuticals in part because current toxicological studies fail to fully predict potential cardiac safety issues during the drug development process. Recent advances in tissue engineering suggest that engineered human cardiac tissue ex vivo could be used as a safety assessment platform for candidate drug compounds. CardioMicroTug features aligned cardiac microtissues anchored to microfabricated cantilevers. These cantilevers report forces generated by the cardiac microtissues in real time, thereby providing a direct readout of human cardiac biomechanical function. The goals of Aim 1 are to demonstrate consistent and reproducible physiologically relevant biomechanical responses in engineered cardiac microtissues. Studies in Aim 2 will evaluate the capability of CardioMicroTug to predict changes in contractility when treated with a panel of known cardiac modulators. These studies will set the stage for further commercial development of CardioMicroTug as a high-throughput in vitro 3D cardiac microtissue assay system for assessing cardiotoxicities of pharmaceutical compounds.